crossing96/oncoscreening huggingface dataset:
A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter associated with risk and progression of bladder cancer.	PURPOSE: Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. We hypothesized that the variants in the CASP8 gene are associated with risk of bladder cancer. EXPERIMENTAL DESIGN: In a hospital-based case-control study of 365 case patients with newly diagnosed bladder transitional cell carcinoma and 368 cancer-free controls frequency-matched by age and sex, we genotyped the functional -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 and assessed its associations with risk of bladder cancer and interaction with tobacco smoking. RESULTS: A significant decreased risk of bladder cancer was found for the CASP8 -652 6N ins/del (adjusted odds ratio, 0.72; 95% confidence interval, 0.53-0.99) and del/del (odds ratio, 0.37; 95% confidence interval, 0.18-0.77) genotypes. Furthermore, a significant additive interaction between CASP8 polymorphism and tobacco smoking on bladder cancer risk was observed. CONCLUSIONS: These results suggested that the CASP8 -652 6N ins/del polymorphism is involved in etiology of bladder cancer and thus may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Larger studies are warranted to validate our findings.	bladder
The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers.	PURPOSE: Metastasis remains the main cause of death in both bladder (BCa) and prostate (PCa) cancers. The results of chemotherapy did not show any significant improvement of the survival the past years. Cancer research has led to the identification of signaling pathways involved and molecular targets that could change the natural history. The epithelial-mesenchymal transition (EMT), critical during embryonic development, becomes potentially destructive in many epithelial tumors progression where it is inappropriately activated. The cell-cell and cell-extracellular matrix interactions are altered to release cancer cells, which are able to migrate toward metastatic sites. Hallmarks of EMT include the down-regulation of E-cadherin expression, which is the main component of the adherens junctions. The protein TWIST is a transcriptional repressor of E-cadherin, tumor progression, and metastasis, and could be used as a molecular target to restore the chemosensitivity in BCa and PCa. MATERIALS AND METHODS: We selected the last 5-year basic research literature on EMT and TWIST but also clinical studies on BCa and PCa in which TWIST is overexpressed and could be considered as an efficient prognostic marker and molecular target. RESULTS: TWIST is considered as a potential oncogene promoting the proliferation and inhibiting the apoptosis. TWIST promotes the synthesis of the pro-angiogenic factor, vascular endothelial growth factor (VEGF) involved in tumor progression and metastasis. Apoptosis and angiogenesis are two essential cancer progression steps in many epithelial tumors, including BCa and PCa. CONCLUSIONS: With the targeted therapy, oncology has entered into a new era, which is going to be critical in cancer treatment in combination with traditional anticancer drugs.	bladder
Economic aspects of bladder cancer: what are the benefits and costs?	OBJECTIVE: Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic and human toll of this disease. The purpose of this paper was to utilize the recent literature to identify opportunities for improving the benefits and costs of BC care. METHODS: A PubMed search was performed of recent publications concerning (BC) cost-effectiveness. We reviewed studies, reviews, opinion papers and cost-effectiveness analyses, focusing primarily on non-muscle-invasive bladder cancer (Ta/T1; NMIBC). RESULTS: New diagnostic tools such as urine markers may assist in more cost-effectively detecting BC at an earlier stage, however, these markers cannot replace the cystoscopy, which is the current standard of care. A photodynamic diagnostic tool (PDD) using hexylaminolevulinate (Hexvix) enhances tumor visibility and improves transurethral resection of bladder cancer (TURB) results, potentially reducing recurrence rates and lowering treatment costs. While the importance of BC research has been acknowledged, research investment has been continuously reduced during the last 5 years. CONCLUSIONS: The economic burden of BC is well-characterized in the literature. This study suggests that new technologies (i.e., urine-based tests, PDD) and therapeutic regimes (intravesical chemotherapy, adjuvant immunotherapy) have significant potential to improve the diagnosis, treatment and on-going monitoring of BC patients, with potential improvements in clinical outcomes and concurrent cost-savings. A renewed interest and investment in BC research are required to ensure future advancements.	bladder
Bladder cancer in the elderly: clinical outcomes, basic mechanisms, and future research direction.	The association between aging and cancer is well exemplified by bladder cancer: with advancing age, the risk of developing bladder cancer increases, and patients' clinical presentation and outcomes worsen. Care for elderly patients with bladder cancer requires specific knowledge of many key geriatric clinical issues in order to determine optimal treatment plans. While numerous studies have tried to address the role of urologic intervention for elderly patients with bladder cancer, many studies fail to incorporate a component of true functional assessment. Evaluation tools that incorporate comorbidities, disabilities and functional status will need to be developed, as chronological age is a poor predictor of treatment outcomes. Additionally, further research is necessary to better understand the basic mechanisms that predispose elderly patients to develop this costly and life-threatening disease. This Review examines the current literature evaluating the clinical and mechanistic interactions between aging and bladder cancer, and suggests the formulation of a research agenda to address the issues raised.	bladder
Inactivation of p53 and Pten promotes invasive bladder cancer.	Although bladder cancer represents a serious health problem worldwide, relevant mouse models for investigating disease progression or therapeutic targets have been lacking. We show that combined deletion of p53 and Pten in bladder epithelium leads to invasive cancer in a novel mouse model. Inactivation of p53 and PTEN promotes tumorigenesis in human bladder cells and is correlated with poor survival in human tumors. Furthermore, the synergistic effects of p53 and Pten deletion are mediated by deregulation of mammalian target of rapamycin (mTOR) signaling, consistent with the ability of rapamycin to block bladder tumorigenesis in preclinical studies. Our integrated analyses of mouse and human bladder cancer provide a rationale for investigating mTOR inhibition for treatment of patients with invasive disease.	bladder
[Hexvix induced fluorescence blue light cystoscopy--a new perspective in superficial bladder tumors diagnosis].	INTRODUCTION: The aim of our study was to establish the place of Hexvix blue light cystoscopy (BLC) in superficial bladder tumors (SBT) diagnosis and to compare it with standard white light cystoscopy (WLC). MATERIAL AND METHODS: Between December 2007 and February 2008, WLC and BLC and transurethral bladder resection (TURB) of all apparent detected lesions were performed in 25 cases. The patients diagnosed with superficial bladder tumors have been followed-up after 18 weeks by WLC and BLC. The control group included the same number of consecutive patients with SBT, diagnosed only by WLC, which underwent the same treatment and follow-up protocol as the study group. RESULTS: WLC identified 40 suspicious lesions (37 pathologically confirmed), while BLC detected 58 apparent tumors (52 pathologically confirmed). So, from the 54 tumors with positive histology, WLC correctly diagnosed 68.5%, with a rate of 7.5% false-positive results, while BLC diagnosed 96.3%, presenting a 10.3% rate of false-positive results. 22 cases of the study group diagnosed with SBT were followed. The tumor recurrence rate after 18 weeks was 4.5% for the study group and 22.7% for the control group. CONCLUSIONS: Hexvix fluorescence cystoscopy is a valuable diagnostic method, with considerably better results by comparison to WLC. The improved diagnostic accuracy may have a significant impact upon the recurrence rate.	bladder
Bladder cancer: new TUR techniques.	Transurethral resection of bladder tumours (TURBT) using a wire loop remains the gold-standard treatment for bladder tumours, but it is associated with unacceptably high early recurrence rates after first resection. Improvements to standard resection techniques and a range of optical and technological advances offer exciting possibilities for improving outcomes. Early second resection has been shown to reduce recurrence rates, and increase response to intravesical chemotherapy and/or immunotherapy. It should be considered in most high-risk non-muscle invasive cancers (T1; G3; multifocal) being managed by bladder conservation. Newer energy sources, such as laser, may facilitate day case management of bladder tumours using local anaesthesia in select groups of patients. The novel technique of photodynamic diagnosis improves tumour detection, and quality of resection, and is likely to become the standard for initial tumour management. The traditional 'incise and scatter' resection technique goes against all oncological surgical principles. En-bloc resection of tumours would be far preferable and demands further development and evaluation. The technique of TURBT needs to evolve to allow first-time clearance of disease and low recurrence rates.	bladder
Study of interaction of hypericin and its pharmaceutical preparation by fluorescence techniques.	We report the detection of interactions between a photosensitizer, hypericin (HY), and its solvent system prepared with a formulation additive, polyvinylpyrrolidone (PVP), a commonly used pharmaceutical excipient. Fluorescence correlation spectroscopy (FCS) and fluorescence lifetime imaging microscopy (FLIM) were used to study aggregation and binding of HY in the presence of PVP. Digitized fluorescence endoscopic imaging (DFEI) was used to study the effect of the pharmaceutical formulation in the in vivo tumor implanted chick chorioallantoic membrane (CAM) model. The results presented reveal the coordination of HY-PVP binding, HY disaggregation in the presence of PVP, and strengthened HY tumor uptake selectivity. PVP is thus suggested as a potential adjuvant to previously investigated N-methyl pyrrolidone (NMP) in the HY delivery system as well as a replacement for the conventionally used albumin in the HY bladder instillation fluids preparation for clinical use.	bladder
Bladder cancer SNP panel predicts susceptibility and survival.	Bladder cancer is the fourth most common malignancy in men and the eighth most common in women in western countries. Single nucleotide polymorphisms (SNPs) in genes that regulate telomere maintenance, mitosis, inflammation, and apoptosis have not been assessed extensively for this disease. Using a population-based study with 832 bladder cancer cases and 1,191 controls, we assessed genetic variation in relation to cancer susceptibility or survival. Findings included an increased risk associated with variants in the methyl-metabolism gene, MTHFD2 (OR 1.7 95% CI 1.3-2.3), the telomerase TEP1 (OR 1.8 95% CI 1.2-2.6) and decreased risk associated with the inflammatory response gene variant IL8RB (OR 0.6 95% CI 0.5-0.9) compared to wild-type. Shorter survival was associated with apoptotic gene variants, including CASP9 (HR 1.8 95% CI 1.1-3.0). Variants in the detoxification gene EPHX1 experienced longer survival (HR 0.4 (95% CI 0.2-0.8). These genes can now be assessed in multiple study populations to identify and validate SNPs appropriate for clinical use.	bladder
Differential expression of immunohistochemical markers in bladder smooth muscle and myofibroblasts, and the potential utility of desmin, smoothelin, and vimentin in staging of bladder carcinoma.	Distinguishing bladder muscularis propria from muscularis mucosae can be problematic especially in transurethral resection specimens performed for bladder carcinoma. Moreover, bladder carcinoma can be associated with a proliferative/desmoplastic myofibroblastic response that can resemble smooth muscle and potentially lead to overdiagnosis of muscularis propria invasion. The aim of this study was to investigate the potential role of immunohistochemistry in staging bladder carcinoma by evaluating the expression of different markers in myofibroblasts and nonvascular smooth muscle cells in 15 cases of invasive bladder carcinoma. Reactive myofibroblasts were consistently positive for vimentin and smooth muscle actin, consistently negative for caldesmon, desmin, and smoothelin, and had variable expression of actin and CD10. Nonvascular smooth muscle cells of the bladder were consistently positive for smooth muscle actin, actin, desmin, and caldesmon, and consistently negative for CD10. In contrast to smooth muscle cells of the muscularis propria, which displayed strong smoothelin expression in all 15 cases, the smooth muscle cells of the muscularis mucosae displayed moderate smoothelin expression in only 1 (9%) of 11 cases (P=10(-7)). Surprisingly, although strongly highlighting endothelial and endomysial cells, the smooth muscle cells of the muscularis propria weakly expressed vimentin in only 1 (7%) of 15 cases, whereas smooth muscle cells of the muscularis mucosae had moderate or strong expression in 9 (82%) of 11 cases (P=0.00016). The sensitivity and specificity of desmin or caldesmon expression for smooth muscle cells were 100%. The sensitivity and specificity of strong smoothelin expression for muscularis propria were 100%, whereas those of absent vimentin expression were 93 and 82%, respectively. Although morphology remains the gold standard, the findings suggest that immunohistochemistry, using a panel composed of desmin, smoothelin, and vimentin, may be potentially useful for staging of bladder carcinoma. Confirmatory larger-scale studies, especially on transurethral resection specimens, are warranted.	bladder
Genitourinary long-term outcomes for childhood cancer survivors.	The treatment of pediatric malignancies represents one of the success stories of modern medicine. As survival has increased, the focus is now on minimizing harmful effects of treatment. There continue to be late toxicities and secondary malignancies of the genitourinary (GU) system for childhood cancer survivors related to the specific therapeutic exposures. A systematic approach is important for prevention and treatment of these adverse late GU effects.	bladder
Routine surveillance cystoscopy for patients with augmentation and substitution cystoplasty for benign urological conditions: is it necessary?	OBJECTIVE: To evaluate screening cystoscopy as the long-term follow up in patients with an enterocystoplasty for > or =10 years. PATIENTS AND METHODS: We performed a prospective analysis of 92 consecutive patients who attended our endoscopy suite for regular check cystoscopy as per standard follow-up. This is performed for all patients with cystoplasty performed at our institute after 10 years. The data were recorded on patient demographics, original diagnosis and type of cystoplasty. In all, 53 of these patients consented to undergo bladder biopsies at the same time. RESULTS: The median (range) follow-up was 15 (10-33) years. No cancer was identified with either surveillance cystoscopy or on routine biopsies. Chronic inflammation was identified in 25 biopsies (27%). Villous atrophy was present in 12 (55%) ileal patch and three (12.5%) colonic patch biopsies. During this study, the first and only case of malignancy in a cystoplasty at our institution was diagnosed in a symptomatic patient. She had intermittent haematuria and recurrent urinary tract infections (UTIs). She previously had a normal surveillance cystoscopy. CONCLUSIONS: We feel that it is not necessary to perform yearly check cystoscopies in patients with augmented bladders at least in the first 15 years, as cancer has not yet been detected with surveillance cystoscopy in this patient group. However, if the patient develops haematuria or other worrisome symptoms including suprapubic pain and recurrent unexplained UTIs a full evaluation, including cystoscopy and computerized tomography should be undertaken.	bladder
Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.	Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value the expected proportion of false discoveries (q-value). Haplotype analysis revealed significant associations (P < 0.01) between bladder cancer and two genes (POLB and FANCA) with an associated q-value of 24%. A permutation test was also used to determine whether, in each pathway analyzed, there are more variants whose allelic frequencies are different between cases and controls as compared with what would be expected by chance. Differences were found for cell cycle regulation (P = 0.02) and to a lesser extent for DSBR (P = 0.05) pathways. These results hint to a few potential candidate genes; however, our study was limited by the small sample size and therefore low statistical power to detect associations. It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours.	bladder
Interleukin-10 G-1082A and C-819T polymorphisms as possible molecular markers of urothelial bladder cancer.	BACKGROUND AND AIMS: Interleukin-10 (IL-10) is an immunosuppressive cytokine that may promote tumor growth and metastasis in later stages of cancer development. DNA sequence variations in IL-10 gene may lead to altered production and/or activity, and this can modulate an individual's susceptibility to urothelial bladder cancer (UBC). To test this hypothesis, we investigated the association of rs 1800896 and rs 3021097 polymorphisms in IL-10 gene and their haplotypes with the risk of UBC in a Northern Indian population. METHODS: We analyzed two single nucleotide polymorphisms of IL-10 gene at G-1082A (rs 1800896) and C-819T (rs 3021097) in 214 histologically confirmed UBC patients and 385 matched controls by allele-specific polymerase chain reaction (AS-PCR). RESULTS: IL-10 C-819T CT, TT genotypes and T carriers (CT + TT) had significant association with UBC susceptibility (OR 1.75, 95% CI 1.09-2.80; OR 1.81, 95% CI 1.09-3.01 and OR 1.77, 95% CI 1.14-2.75, respectively). Similarly, GA, AA genotypes and A carriers (G-1082A) demonstrated increased risk for UBC (OR 1.91, 95% CI 1.04-3.50; OR 2.01, 95% CI 1.08-3.74 and OR 1.95, 95% CI 1.09-3.50, respectively). TT (C-819T) and T carriers showed protective association with high-risk tumors; (OR 0.34, 95% CI 0.13-0.88 and OR 0.41, 95% CI 0.17-0.97, respectively). We did not observe any association of IL-10 polymorphisms with smoking habits and UBC risk. CONCLUSIONS: The study suggested that the low-producing genotypes of IL-10 (C-819T and G-1082A) polymorphisms are associated with increased UBC risk. Individuals with (C-819T) TT genotype and T carriers, however, showed a protective association with high-risk tumors. Our data suggest that IL-10 G-1082A and C-819T polymorphisms may be used as a molecular marker of urothelial bladder cancer.	bladder
Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer.	This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemotherapeutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community.	bladder
Active surveillance of low grade bladder tumors.	OBJECTIVE: This study was done in order to evaluate the safety of an active surveillance program, without resection of the tumor, in patients with recurrent small bladder cancer. PATIENTS AND METHODS: Active surveillance was offered to patients with small (<10 mm) papillary, asymptomatic tumor(s) with negative urinary cytology that was found on routine follow-up in patients who had previous resection(s) of superficial (Ta) low-grade (G1-2) bladder tumor(s). The surveillance protocol included cystoscopy and urinary cytology every 3 months for 2 years and then every 6 months. Surveillance was stopped and the patient referred to transurethral tumor resection if the patient had developed either symptoms related to the tumor, or positive cytology, or if there has been a significant alteration in tumor morphology, size or upon patient's request. RESULTS: 43 active surveillance periods were documented in 31 patients (mean age 68 years). Mean period length was 16.1 months (S.D. 15.7 months and range 3-60 months). 35 surveillance periods were terminated with tumor resection and 8 patients are still under surveillance. The main reasons for termination of surveillance were the appearance of additional tumors (15 events), excessive tumor growth (12 events) and patient's request (7 events). All resected tumors were stage Ta except a single case of stage T1. CONCLUSIONS: Recurrent papillary bladder tumors in patients with history of low grade Ta tumor(s) pose minimal risk for the patient. An active surveillance policy, without immediate resection of the tumor may be considered in these cases.	bladder
Updates in intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer.	Electromotive drug administration (EMDA) increases the local drug efficacy by controlling and enhancing transmembranous transport into tissue. EMDA of intravesical mitomycin-C (MMC) has been used for treatment of non-muscle invasive bladder cancer (NMIBC) for about a decade on the basis of laboratory studies that demonstrated an enhanced administration rate of MMC into all bladder wall layers after EMDA compared to standard instillation/passive diffusion (PD). Higher MMC concentrations might have a clinical impact since EMDA was associated with lower recurrence rates than PD in randomized studies. Further data suggest that EMDA/MMC is at least equivalent to BCG in treatment of high-risk bladder tumours. In addition, BCG combined with EMDA/MMC as well as preoperative EMDA/MMC are new therapeutic strategies with promising preliminary results in terms of higher remission rates and longer remission times. In summary, these findings suggest that EMDA for MMC delivery in the bladder could be a major therapeutic breakthrough in the treatment of NMIBC.	bladder